Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Review

Tumor-associated macrophages: from basic research to clinical application

Authors: Li Yang, Yi Zhang

Published in: Journal of Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

The fact that various immune cells, including macrophages, can be found in tumor tissues has long been known. With the introduction of concept that macrophages differentiate into a classically or alternatively activated phenotype, the role of tumor-associated macrophages (TAMs) is now beginning to be elucidated. TAMs act as “protumoral macrophages,” contributing to disease progression. TAMs can promote initiation and metastasis of tumor cells, inhibit antitumor immune responses mediated by T cells, and stimulate tumor angiogenesis and subsequently tumor progression. As the relationship between TAMs and malignant tumors becomes clearer, TAMs are beginning to be seen as potential biomarkers for diagnosis and prognosis of cancers, as well as therapeutic targets in these cases. In this review, we will discuss the origin, polarization, and role of TAMs in human malignant tumors, as well as how TAMs can be used as diagnostic and prognostic biomarkers and therapeutic targets of cancer in clinics.
Literature
1.
go back to reference Tu Z, Xiao R, Xiong J, Tembo KM, Deng X, Xiong M, Liu P, Wang M, Zhang Q. CCR9 in cancer: oncogenic role and therapeutic targeting. Hematol Oncol. 2016;9:10.CrossRef Tu Z, Xiao R, Xiong J, Tembo KM, Deng X, Xiong M, Liu P, Wang M, Zhang Q. CCR9 in cancer: oncogenic role and therapeutic targeting. Hematol Oncol. 2016;9:10.CrossRef
3.
go back to reference Teng F, Tian WY, Wang YM, Zhang YF, Guo F, Zhao J, Gao C, Xue FX. Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. J Hematol Oncol. 2016;9:8.CrossRefPubMedPubMedCentral Teng F, Tian WY, Wang YM, Zhang YF, Guo F, Zhao J, Gao C, Xue FX. Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. J Hematol Oncol. 2016;9:8.CrossRefPubMedPubMedCentral
5.
go back to reference Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol. 2017;10:36.CrossRefPubMedPubMedCentral Chen Y, Zhang S, Wang Q, Zhang X. Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol. 2017;10:36.CrossRefPubMedPubMedCentral
7.
go back to reference Van Overmeire E, Laoui D, Keirsse J, Bonelli S, Lahmar Q, Van Ginderachter JA. STAT of the union: dynamics of distinct tumor-associated macrophage subsets governed by STAT1. Eur J Immunol. 2014;44:2238–42.CrossRefPubMed Van Overmeire E, Laoui D, Keirsse J, Bonelli S, Lahmar Q, Van Ginderachter JA. STAT of the union: dynamics of distinct tumor-associated macrophage subsets governed by STAT1. Eur J Immunol. 2014;44:2238–42.CrossRefPubMed
8.
go back to reference De I, Steffen MD, Clark PA, Patros CJ, Sokn E, Bishop SM, Litscher S, Maklakova VI, Kuo JS, Rodriguez FJ, et al. CSF1 overexpression promotes high-grade glioma formation without impacting the polarization status of glioma-associated microglia and macrophages. Cancer Res. 2016;76:2552–60.CrossRefPubMed De I, Steffen MD, Clark PA, Patros CJ, Sokn E, Bishop SM, Litscher S, Maklakova VI, Kuo JS, Rodriguez FJ, et al. CSF1 overexpression promotes high-grade glioma formation without impacting the polarization status of glioma-associated microglia and macrophages. Cancer Res. 2016;76:2552–60.CrossRefPubMed
9.
go back to reference Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO. The cellular and molecular origin of tumor-associated macrophages. Science. 2014;344:921–5.CrossRefPubMedPubMedCentral Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO. The cellular and molecular origin of tumor-associated macrophages. Science. 2014;344:921–5.CrossRefPubMedPubMedCentral
10.
go back to reference Linde N, Lederle W, Depner S, van Rooijen N, Gutschalk CM, Mueller MM. Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol. 2012;227:17–28.CrossRefPubMed Linde N, Lederle W, Depner S, van Rooijen N, Gutschalk CM, Mueller MM. Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol. 2012;227:17–28.CrossRefPubMed
11.
go back to reference Su S, Liu Q, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25:605–20.CrossRefPubMed Su S, Liu Q, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25:605–20.CrossRefPubMed
12.
go back to reference Nandi B, Shapiro M, Samur MK, Pai C, Frank NY, Yoon C, Prabhala RH, Munshi NC, Gold JS. Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages. Oncoimmunology. 2016;5:e1189052.CrossRefPubMed Nandi B, Shapiro M, Samur MK, Pai C, Frank NY, Yoon C, Prabhala RH, Munshi NC, Gold JS. Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages. Oncoimmunology. 2016;5:e1189052.CrossRefPubMed
13.
go back to reference Mota JM, Leite CA, Souza LE, Melo PH, Nascimento DC, De-Deus-Wagatsuma VM, Temporal J, Figueiredo F, Noushmehr H, Alves-Filho JC, et al. Post-sepsis state induces tumor-associated macrophage accumulation through CXCR4/CXCL12 and favors tumor progression in mice. Cancer Immunol Res. 2016;4:312–22.CrossRefPubMed Mota JM, Leite CA, Souza LE, Melo PH, Nascimento DC, De-Deus-Wagatsuma VM, Temporal J, Figueiredo F, Noushmehr H, Alves-Filho JC, et al. Post-sepsis state induces tumor-associated macrophage accumulation through CXCR4/CXCL12 and favors tumor progression in mice. Cancer Immunol Res. 2016;4:312–22.CrossRefPubMed
15.
go back to reference Wang H, Shao Q, Sun J, Ma C, Gao W, Wang Q, Zhao L, Qu X. Interactions between colon cancer cells and tumor-infiltrated macrophages depending on cancer cell-derived colony stimulating factor 1. Oncoimmunology. 2016;5:e1122157.CrossRefPubMedPubMedCentral Wang H, Shao Q, Sun J, Ma C, Gao W, Wang Q, Zhao L, Qu X. Interactions between colon cancer cells and tumor-infiltrated macrophages depending on cancer cell-derived colony stimulating factor 1. Oncoimmunology. 2016;5:e1122157.CrossRefPubMedPubMedCentral
16.
go back to reference Li Y, Zheng Y, Li T, Wang Q, Qian J, Lu Y, Zhang M, Bi E, Yang M, Reu F, et al. Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma. Oncotarget. 2015;6:24218–29.CrossRefPubMedPubMedCentral Li Y, Zheng Y, Li T, Wang Q, Qian J, Lu Y, Zhang M, Bi E, Yang M, Reu F, et al. Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma. Oncotarget. 2015;6:24218–29.CrossRefPubMedPubMedCentral
17.
go back to reference Ambade A, Satishchandran A, Saha B, Gyongyosi B, Lowe P, Kodys K, Catalano D, Szabo G. Hepatocellular carcinoma is accelerated by NASH involving M2 macrophage polarization mediated by hif-1α induced IL-10. Oncoimmunology. 2016;5:e1221557.CrossRefPubMed Ambade A, Satishchandran A, Saha B, Gyongyosi B, Lowe P, Kodys K, Catalano D, Szabo G. Hepatocellular carcinoma is accelerated by NASH involving M2 macrophage polarization mediated by hif-1α induced IL-10. Oncoimmunology. 2016;5:e1221557.CrossRefPubMed
18.
go back to reference Zhao P, Gao D, Wang Q, Song B, Shao Q, Sun J, Ji C, Li X, Li P, Qu X. Response gene to complement 32 (RGC-32) expression on M2-polarized and tumor-associated macrophages is M-CSF-dependent and enhanced by tumor-derived IL-4. Cell Mol Immunol. 2015;12:692–9.CrossRefPubMed Zhao P, Gao D, Wang Q, Song B, Shao Q, Sun J, Ji C, Li X, Li P, Qu X. Response gene to complement 32 (RGC-32) expression on M2-polarized and tumor-associated macrophages is M-CSF-dependent and enhanced by tumor-derived IL-4. Cell Mol Immunol. 2015;12:692–9.CrossRefPubMed
19.
go back to reference Ma R, Ji T, Chen D, Dong W, Zhang H, Yin X, Ma J, Liang X, Zhang Y, Shen G, et al. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression. Oncoimmunology. 2016;5:e1118599.CrossRefPubMedPubMedCentral Ma R, Ji T, Chen D, Dong W, Zhang H, Yin X, Ma J, Liang X, Zhang Y, Shen G, et al. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression. Oncoimmunology. 2016;5:e1118599.CrossRefPubMedPubMedCentral
20.
go back to reference Cha HR, Lee JH, Hensel JA, Sawant AB, Davis BH, Lee CM, Deshane JS, Ponnazhagan S. Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. Prostate. 2016;76:624–36.CrossRefPubMed Cha HR, Lee JH, Hensel JA, Sawant AB, Davis BH, Lee CM, Deshane JS, Ponnazhagan S. Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. Prostate. 2016;76:624–36.CrossRefPubMed
21.
go back to reference Tripathi C, Tewari BN, Kanchan RK, Baghel KS, Nautiyal N, Shrivastava R, Kaur H, Bhatt ML, Bhadauria S. Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2-polarized phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin. Oncotarget. 2014;5:5350–68.CrossRefPubMedPubMedCentral Tripathi C, Tewari BN, Kanchan RK, Baghel KS, Nautiyal N, Shrivastava R, Kaur H, Bhatt ML, Bhadauria S. Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2-polarized phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin. Oncotarget. 2014;5:5350–68.CrossRefPubMedPubMedCentral
22.
go back to reference Xiao G, Wang X, Sheng J, Lu S, Yu X, Wu JD. Soluble NKG2D ligand promotes MDSC expansion and skews macrophage to the alternatively activated phenotype. J Hematol Oncol. 2015;8:13.CrossRefPubMedPubMedCentral Xiao G, Wang X, Sheng J, Lu S, Yu X, Wu JD. Soluble NKG2D ligand promotes MDSC expansion and skews macrophage to the alternatively activated phenotype. J Hematol Oncol. 2015;8:13.CrossRefPubMedPubMedCentral
23.
go back to reference Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Gene Dev. 2010;24:241–55.CrossRefPubMedPubMedCentral Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Gene Dev. 2010;24:241–55.CrossRefPubMedPubMedCentral
24.
go back to reference DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16:91–102.CrossRefPubMedPubMedCentral DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16:91–102.CrossRefPubMedPubMedCentral
25.
go back to reference Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S, Korets L, Lam J, Tawfik D, DeNardo DG, et al. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell. 2010;17:121–34.CrossRefPubMedPubMedCentral Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S, Korets L, Lam J, Tawfik D, DeNardo DG, et al. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell. 2010;17:121–34.CrossRefPubMedPubMedCentral
26.
go back to reference Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. Int J Clin Exp Med. 2011;208:479–90. Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. Int J Clin Exp Med. 2011;208:479–90.
27.
go back to reference Yamada K, Uchiyama A, Uehara A, Perera B, Ogino S, Yokoyama Y, Takeuchi Y, Udey MC, Ishikawa O, Motegi S. MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cell-induced angiogenesis and M2 polarization of tumor-associated macrophages. Cancer Res. 2016;76:4283–92.CrossRefPubMed Yamada K, Uchiyama A, Uehara A, Perera B, Ogino S, Yokoyama Y, Takeuchi Y, Udey MC, Ishikawa O, Motegi S. MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cell-induced angiogenesis and M2 polarization of tumor-associated macrophages. Cancer Res. 2016;76:4283–92.CrossRefPubMed
28.
go back to reference Yaddanapudi K, Putty K, Rendon BE, Lamont GJ, Faughn JD, Satoskar A, Lasnik A, Eaton JW, Mitchell RA. Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. J Immunol. 2013;190:2984–93.CrossRefPubMedPubMedCentral Yaddanapudi K, Putty K, Rendon BE, Lamont GJ, Faughn JD, Satoskar A, Lasnik A, Eaton JW, Mitchell RA. Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. J Immunol. 2013;190:2984–93.CrossRefPubMedPubMedCentral
29.
go back to reference Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol. 2000;164:762–7.CrossRefPubMed Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol. 2000;164:762–7.CrossRefPubMed
30.
go back to reference Sánchez-Martín L, Estecha A, Samaniego R, Sánchez-Ramón S, Vega MÁ, Sánchez-Mateos P. The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood. 2011;117:88–97.CrossRefPubMed Sánchez-Martín L, Estecha A, Samaniego R, Sánchez-Ramón S, Vega MÁ, Sánchez-Mateos P. The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood. 2011;117:88–97.CrossRefPubMed
31.
go back to reference Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG, Coussens LM, Karin M, Goldrath AW, Johnson RS. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 2010;70:7465–75.CrossRefPubMedPubMedCentral Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG, Coussens LM, Karin M, Goldrath AW, Johnson RS. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 2010;70:7465–75.CrossRefPubMedPubMedCentral
32.
go back to reference Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457:102–6.CrossRefPubMedPubMedCentral Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457:102–6.CrossRefPubMedPubMedCentral
33.
go back to reference Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10:712–23.CrossRefPubMed Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10:712–23.CrossRefPubMed
34.
go back to reference Raggi C, Mousa HS, Correnti M, Sica A, Invernizzi P. Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting strategies. Oncogene. 2016;35:671–82.CrossRefPubMed Raggi C, Mousa HS, Correnti M, Sica A, Invernizzi P. Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting strategies. Oncogene. 2016;35:671–82.CrossRefPubMed
35.
go back to reference Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491:254–8.PubMedPubMedCentral Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491:254–8.PubMedPubMedCentral
36.
go back to reference Greten FR, Karin M. The IKK/NF-kappaB activation pathway—a target for prevention and treatment of cancer. Cancer Lett. 2004;206:193–9.CrossRefPubMed Greten FR, Karin M. The IKK/NF-kappaB activation pathway—a target for prevention and treatment of cancer. Cancer Lett. 2004;206:193–9.CrossRefPubMed
37.
go back to reference Kong L, Zhou Y, Bu H, Lv T, Shi Y, Yang J. Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice. J Exp Clin Canc Res. 2016;35:131.CrossRef Kong L, Zhou Y, Bu H, Lv T, Shi Y, Yang J. Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice. J Exp Clin Canc Res. 2016;35:131.CrossRef
38.
go back to reference Lu T, Ramakrishnan R, Altiok S, Youn JI, Cheng P, Celis E, Pisarev V, Sherman S, Sporn MB, Gabrilovich D. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest. 2011;121:4015–29.CrossRefPubMedPubMedCentral Lu T, Ramakrishnan R, Altiok S, Youn JI, Cheng P, Celis E, Pisarev V, Sherman S, Sporn MB, Gabrilovich D. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest. 2011;121:4015–29.CrossRefPubMedPubMedCentral
39.
go back to reference Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206:1327–37.CrossRefPubMedPubMedCentral Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206:1327–37.CrossRefPubMedPubMedCentral
40.
go back to reference Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254–65.CrossRefPubMed Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254–65.CrossRefPubMed
41.
go back to reference Chen J, Yao Y, Gong C, Yu F, Su S, Chen J, Liu B, Deng H, Wang F, Lin L, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell. 2011;19:541–55.CrossRefPubMedPubMedCentral Chen J, Yao Y, Gong C, Yu F, Su S, Chen J, Liu B, Deng H, Wang F, Lin L, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell. 2011;19:541–55.CrossRefPubMedPubMedCentral
42.
go back to reference Finkernagel F, Reinartz S, Lieber S, Adhikary T, Wortmann A, Hoffmann N, Bieringer T, Nist A, Stiewe T, Jansen JM, et al. The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. Oncotarget. 2016; doi: 10.18632/oncotarget.12180 Finkernagel F, Reinartz S, Lieber S, Adhikary T, Wortmann A, Hoffmann N, Bieringer T, Nist A, Stiewe T, Jansen JM, et al. The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. Oncotarget. 2016; doi: 10.​18632/​oncotarget.​12180
43.
go back to reference Deng YR, Liu WB, Lian ZX, Li X, Hou X. Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma. Oncotarget. 2016;7:38292–305.PubMedPubMedCentral Deng YR, Liu WB, Lian ZX, Li X, Hou X. Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma. Oncotarget. 2016;7:38292–305.PubMedPubMedCentral
44.
go back to reference Tomita T, Sakurai Y, Ishibashi S, Maru Y. Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis. Oncogene. 2010;30:3429–39.CrossRef Tomita T, Sakurai Y, Ishibashi S, Maru Y. Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis. Oncogene. 2010;30:3429–39.CrossRef
46.
go back to reference Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A, Politi LS, Gentner B, Brown JL, Naldini L, et al. Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011;19:512–26.CrossRefPubMed Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A, Politi LS, Gentner B, Brown JL, Naldini L, et al. Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011;19:512–26.CrossRefPubMed
47.
go back to reference Wang F, Yang L, Gao Q, Huang L, Wang L, Wang J, Wang S, Zhang B, Zhang Y. CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion. Cancer Immunol Immunother. 2015;64:965–76.CrossRefPubMed Wang F, Yang L, Gao Q, Huang L, Wang L, Wang J, Wang S, Zhang B, Zhang Y. CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion. Cancer Immunol Immunother. 2015;64:965–76.CrossRefPubMed
48.
go back to reference Andersen MN, Abildgaard N, Maniecki MB, Møller HJ, Andersen NF. Monocyte/macrophage-derived soluble CD163: a novel biomarker in multiple myeloma. Eur J Haematol. 2014;93:41–7.CrossRefPubMed Andersen MN, Abildgaard N, Maniecki MB, Møller HJ, Andersen NF. Monocyte/macrophage-derived soluble CD163: a novel biomarker in multiple myeloma. Eur J Haematol. 2014;93:41–7.CrossRefPubMed
49.
go back to reference Tang X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett. 2013;332:3–10.CrossRefPubMed Tang X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett. 2013;332:3–10.CrossRefPubMed
50.
go back to reference Adams DL, Martin SS, Alpaugh RK, Charpentier M, Tsai S, Bergan RC, Ogden IM, Catalona W, Chumsri S, Tang CM, et al. Circulating giant macrophages as a potential biomarker of solid tumors. Proc Natl Acad Sci U S A. 2014;111:3514–9.CrossRefPubMedPubMedCentral Adams DL, Martin SS, Alpaugh RK, Charpentier M, Tsai S, Bergan RC, Ogden IM, Catalona W, Chumsri S, Tang CM, et al. Circulating giant macrophages as a potential biomarker of solid tumors. Proc Natl Acad Sci U S A. 2014;111:3514–9.CrossRefPubMedPubMedCentral
51.
go back to reference Yang L, Wang F, Wang L, Huang L, Wang J, Zhang B, Zhang Y. CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget. 2015;6:10592–603.CrossRefPubMedPubMedCentral Yang L, Wang F, Wang L, Huang L, Wang J, Zhang B, Zhang Y. CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget. 2015;6:10592–603.CrossRefPubMedPubMedCentral
52.
go back to reference Shigeoka M, Urakawa N, Nakamura T, Nishio M, Watajima T, Kuroda D, Komori T, Kakeji Y, Semba S, Yokozaki H. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci. 2013;104:1112–9.CrossRefPubMed Shigeoka M, Urakawa N, Nakamura T, Nishio M, Watajima T, Kuroda D, Komori T, Kakeji Y, Semba S, Yokozaki H. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci. 2013;104:1112–9.CrossRefPubMed
53.
go back to reference Kim KJ, Wen XY, Yang HK, Kim WH, Kang GH. Prognostic implication of M2 macrophages are determined by the proportional balance of tumor associated macrophages and tumor infiltrating lymphocytes in microsatellite-unstable gastric carcinoma. PLoS One. 2015;10:e0144192.CrossRefPubMedPubMedCentral Kim KJ, Wen XY, Yang HK, Kim WH, Kang GH. Prognostic implication of M2 macrophages are determined by the proportional balance of tumor associated macrophages and tumor infiltrating lymphocytes in microsatellite-unstable gastric carcinoma. PLoS One. 2015;10:e0144192.CrossRefPubMedPubMedCentral
54.
go back to reference Boström MM, Irjala H, Mirtti T, Taimen P, Kauko T, Ålgars A, Jalkanen S, Boström PJ. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS One. 2015;10:e0133552.CrossRefPubMedPubMedCentral Boström MM, Irjala H, Mirtti T, Taimen P, Kauko T, Ålgars A, Jalkanen S, Boström PJ. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS One. 2015;10:e0133552.CrossRefPubMedPubMedCentral
55.
go back to reference Pienta KJ, Machiels JP, Schrijvers D, Alekseev B, Shkolnik M, Crabb SJ, Li S, Seetharam S, Puchalski TA, Takimoto C, et al. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs. 2013;31:760–8.CrossRefPubMed Pienta KJ, Machiels JP, Schrijvers D, Alekseev B, Shkolnik M, Crabb SJ, Li S, Seetharam S, Puchalski TA, Takimoto C, et al. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs. 2013;31:760–8.CrossRefPubMed
56.
go back to reference Brana I, Calles A, LoRusso PM, Yee LK, Puchalski TA, Seetharam S, Zhong B, de Boer CJ, Tabernero J, Calvo E. Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol. 2015;10:111–23.CrossRefPubMed Brana I, Calles A, LoRusso PM, Yee LK, Puchalski TA, Seetharam S, Zhong B, de Boer CJ, Tabernero J, Calvo E. Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol. 2015;10:111–23.CrossRefPubMed
57.
go back to reference Sandhu SK, Papadopoulos K, Fong PC, Patnaik A, Messiou C, Olmos D, Wang G, Tromp BJ, Puchalski TA, Balkwill F, et al. A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol. 2013;71:1041–50.CrossRefPubMed Sandhu SK, Papadopoulos K, Fong PC, Patnaik A, Messiou C, Olmos D, Wang G, Tromp BJ, Puchalski TA, Balkwill F, et al. A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol. 2013;71:1041–50.CrossRefPubMed
58.
go back to reference Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23:249–62.CrossRefPubMed Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23:249–62.CrossRefPubMed
59.
go back to reference Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, Mitchem JB, Plambeck-Suess SM, Worley LA, Goetz BD, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res. 2013;19:3404–15.CrossRefPubMedPubMedCentral Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, Mitchem JB, Plambeck-Suess SM, Worley LA, Goetz BD, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res. 2013;19:3404–15.CrossRefPubMedPubMedCentral
60.
go back to reference Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016;17:651–62.CrossRefPubMed Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016;17:651–62.CrossRefPubMed
61.
go back to reference Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci U S A. 2010;107:8363–8.CrossRefPubMedPubMedCentral Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci U S A. 2010;107:8363–8.CrossRefPubMedPubMedCentral
62.
go back to reference Chai ZT, Zhu XD, Ao JY, Wang WQ, Gao DM, Kong J, Zhang N, Zhang YY, Ye BG, Ma DN, et al. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol. 2015;8:56.CrossRefPubMedPubMedCentral Chai ZT, Zhu XD, Ao JY, Wang WQ, Gao DM, Kong J, Zhang N, Zhang YY, Ye BG, Ma DN, et al. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol. 2015;8:56.CrossRefPubMedPubMedCentral
63.
go back to reference Pyonteck SM, Gadea BB, Wang HW, Gocheva V, Hunter KE, Tang LH, Joyce JA. Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development. Oncogene. 2012;31:1459–67.CrossRefPubMed Pyonteck SM, Gadea BB, Wang HW, Gocheva V, Hunter KE, Tang LH, Joyce JA. Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development. Oncogene. 2012;31:1459–67.CrossRefPubMed
64.
go back to reference Movahedi K, Schoonooghe S, Laoui D, Houbracken I, Waelput W, Breckpot K, Bouwens L, Lahoutte T, De Baetselier P, Raes G, et al. Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages. Cancer Res. 2012;72:4165–77.CrossRefPubMed Movahedi K, Schoonooghe S, Laoui D, Houbracken I, Waelput W, Breckpot K, Bouwens L, Lahoutte T, De Baetselier P, Raes G, et al. Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages. Cancer Res. 2012;72:4165–77.CrossRefPubMed
65.
go back to reference Smahel M, Duskova M, Polakova I, Musil J. Enhancement of DNA vaccine potency against legumain. J Immunother. 2014;37:293–303.CrossRefPubMed Smahel M, Duskova M, Polakova I, Musil J. Enhancement of DNA vaccine potency against legumain. J Immunother. 2014;37:293–303.CrossRefPubMed
66.
go back to reference Pulaski HL, Spahlinger G, Silva IA, McLean K, Kueck AS, Reynolds RK, Coukos G, Conejo-Garcia JR, Buckanovich RJ. Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer. J Transl Med. 2009;7:49.CrossRefPubMedPubMedCentral Pulaski HL, Spahlinger G, Silva IA, McLean K, Kueck AS, Reynolds RK, Coukos G, Conejo-Garcia JR, Buckanovich RJ. Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer. J Transl Med. 2009;7:49.CrossRefPubMedPubMedCentral
67.
go back to reference Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, Olimpio CO, Bonardi C, Garbi A, Lissoni A, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005;65:2964–71.CrossRefPubMed Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, Olimpio CO, Bonardi C, Garbi A, Lissoni A, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005;65:2964–71.CrossRefPubMed
68.
70.
go back to reference Zanganeh S, Hutter G, Spitler R, Lenkov O, Mahmoudi M, Shaw A, Pajarinen JS, Nejadnik H, Goodman S, Moseley M, et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol. 2016;11:986–94.CrossRefPubMedPubMedCentral Zanganeh S, Hutter G, Spitler R, Lenkov O, Mahmoudi M, Shaw A, Pajarinen JS, Nejadnik H, Goodman S, Moseley M, et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol. 2016;11:986–94.CrossRefPubMedPubMedCentral
71.
go back to reference Song M, Liu T, Shi C, Zhang X, Chen X. Bioconjugated manganese dioxide nanoparticles enhance chemotherapy response by priming tumor-associated macrophages toward M1-like phenotype and attenuating tumor hypoxia. ACS Nano. 2016;10:633–47.CrossRefPubMed Song M, Liu T, Shi C, Zhang X, Chen X. Bioconjugated manganese dioxide nanoparticles enhance chemotherapy response by priming tumor-associated macrophages toward M1-like phenotype and attenuating tumor hypoxia. ACS Nano. 2016;10:633–47.CrossRefPubMed
72.
go back to reference Wang Y, Lin YX, Qiao SL, An HW, Ma Y, Qiao ZY, Rajapaksha RP, Wang H. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment. Biomaterials. 2017;112:153–63.CrossRefPubMed Wang Y, Lin YX, Qiao SL, An HW, Ma Y, Qiao ZY, Rajapaksha RP, Wang H. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment. Biomaterials. 2017;112:153–63.CrossRefPubMed
73.
go back to reference Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331:1612–6.CrossRefPubMedPubMedCentral Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331:1612–6.CrossRefPubMedPubMedCentral
74.
go back to reference Johnson P, Challis R, Chowdhury F, Gao Y, Harvey M, Geldart T, Kerr P, Chan C, Smith A, Steven N, et al. Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer Research UK phase I study. Clin Cancer Res. 2015;21:1321–8.CrossRefPubMed Johnson P, Challis R, Chowdhury F, Gao Y, Harvey M, Geldart T, Kerr P, Chan C, Smith A, Steven N, et al. Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer Research UK phase I study. Clin Cancer Res. 2015;21:1321–8.CrossRefPubMed
76.
go back to reference Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 2007;67:9630–6.CrossRefPubMed Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 2007;67:9630–6.CrossRefPubMed
77.
go back to reference Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012;1269:26–33.CrossRefPubMed Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012;1269:26–33.CrossRefPubMed
79.
go back to reference Kushner BH, Cheung IY, Modak S, Kramer K, Ragupathi G, Cheung NK. Phase I trial of a bivalent gangliosides vaccine in combination with beta-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res. 2014;20:1375–82.CrossRefPubMed Kushner BH, Cheung IY, Modak S, Kramer K, Ragupathi G, Cheung NK. Phase I trial of a bivalent gangliosides vaccine in combination with beta-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res. 2014;20:1375–82.CrossRefPubMed
80.
go back to reference Segal NH, Gada P, Senzer N, Gargano MA, Patchen ML, Saltz LB. A phase II efficacy and safety, open-label, multicenter study of imprime PGG injection in combination with cetuximab in patients with stage IV KRAS-mutant colorectal cancer. Clin Colorectal Canc. 2016;15:222–7.CrossRef Segal NH, Gada P, Senzer N, Gargano MA, Patchen ML, Saltz LB. A phase II efficacy and safety, open-label, multicenter study of imprime PGG injection in combination with cetuximab in patients with stage IV KRAS-mutant colorectal cancer. Clin Colorectal Canc. 2016;15:222–7.CrossRef
81.
go back to reference De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23:277–86.CrossRefPubMed De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23:277–86.CrossRefPubMed
82.
go back to reference Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120:694–705.CrossRefPubMedPubMedCentral Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120:694–705.CrossRefPubMedPubMedCentral
83.
go back to reference Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, Belaygorod L, Carpenter D, Collins L, Piwnica-Worms D, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013;73:1128–41.CrossRefPubMed Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, Belaygorod L, Carpenter D, Collins L, Piwnica-Worms D, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013;73:1128–41.CrossRefPubMed
Metadata
Title
Tumor-associated macrophages: from basic research to clinical application
Authors
Li Yang
Yi Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0430-2

Other articles of this Issue 1/2017

Journal of Hematology & Oncology 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine